Growth hormone releasing factor (GRF) has recently been isolated from human islet cell tumor and structurally characterized by Dr. Guillemin and co-workers at the Salk Institute. Science 218, 585-587 (Nov. 5, 1982). The isolation and characterization of GRF while sought for decades was previously unsuccessful due to its presence in very small quantities. Human hypothalamic growth hormone releasing factor (hGRF) has now been found to have the same structure as GRF isolated from islet cell tumor. Bohlen et al. Biochem. and Biophys. Res. Comm., 114(3) 930-936 (1983)
Rivier and coworkers, Nature 300, 276-278(1982) have described the structure of GRF (1-44) and GRF (1-40), respectively, and shown that GRF is specific for the release of growth hormone. These two forms of GRF are identical at the amino (NH.sub.2 --) terminal but differ in the termination point of the carboxy (COOH) terminus. GRF (1-44) is further distinguished in having an amide group at the carboxy terminus.
Rivier and Vale et al., Id. have shown that the biological activity of GRF resides in the NH.sub.2 -terminal portion of the molecule and full intrinsic activity and potency was demonstrated with GRF(1-29)-NH.sub.2 in vitro.
Lance et al., Biochemical and Biophysical Research Communications 119(1), 265-272 (1984) have shown that GRF (1-29)-NH.sub.2 with substitutions of selected amino acids at positions 1, 2 and 3 cause enhanced release of growth hormone (GH) in both pig and rat in vivo. Rivier, J. E. F. et al. in U.S. Pat. No. 4,518,586 disclose various GRF synthetic peptides including the substitution of D-Ala at position 15. Similarly in U.S. Pat. No. 4,528,190 issued July 9, 1985 also discloses various GRF analogs including the substitution of D-Ala at position 15.
Growth in animals is presumably regulated by a cascade of bio-regulatory molecules. The hypothalamus produces GRF which induces pituitary release of growth hormone. Small quantities of GRF have been found to cause substantial pituitary release of growth hormone into the blood. Thus, GRF has great therapeutic utility in those instances where growth hormone is indicated. For example, GRF may be used in the treatment of hypopituitary dwarfism, diabetes due to growth hormone production abnormalities, promotion of wound healing, treatment of burns and retardation of the aging process. Similarly GRF has utility in the agricultural field. Examples of agricultural uses include, enhanced meat production of fowl or animals raised for food such as pigs, cattle or the like to permit earlier marketing or to produce larger animals for similar time on feed or improve the lean to fat ratios. GRF may also stimulate milk production in dairy cows and egg production in chickens.